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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The involvement of phosphatidylcholine (PC) hydrolysis in the regulation of insulin secretion was studied in mouse pancreatic islets prelabelled with [3H]choline. Phospholipase C (PLC) and phospholipase D (PLD) activities were demonstrated and also that of an enzyme that removes both fatty acids from PC and thus catalyses the production of [3H]glycerophosphorylcholine (GroPCho). After 2 min of incubation with 20 mM glucose a 35% increase in the content of [3H]GroPCho was observed in prelabelled islets, whereas the amount of [3H]lysoPC, [3H]phosphorylcholine (PCho) and [3H]choline was unaffected. After 30 min of incubation with 20 mM glucose, 0.2 mM tolbutamide, 40 mM KC1, 10 mM succinic acid monomethyl ester (SME) or 10 mM NaF, a 25-50% increase in [3H]GroPCho was observed. In the presence of 100 microM diazoxide or 35 microM RHC 80267 the glucose activation was attenuated. PLC was stimulated slightly by tolbutamide and 100 microM isoprenaline (isoproterenol), whereas SME decreased the amount of [3H]PCho by 10%. [3H]Choline content was increased by 25-40% in the presence of 0.16 microM 12-O-tetradecanoylphorbol 13-acetate (TPA), 10 mM NaF or 100 microM carbachol. This effect of fluoride was potentiated in the presence of 20 mM glucose. It is concluded that metabolism of PC to GroPCho may be involved in the regulation of glucose-stimulated insulin secretion, and that PLD may participate in insulin secretion evoked by TPA, carbachol and fluoride.
J Mol Endocrinol 1996 Oct
PMID:Production of [3H]choline-labelled metabolites from endogenously 3H-labelled phosphatidylcholine in mouse pancreatic islets. 893 85

Phospholipase D (PLD; EC 3.1.4.4) has been proposed to play a pivotal role in various cellular processes, but molecular understanding of this enzyme is rather limited. This report describes the nucleotide sequence, structure, and genomic organization of a PLD gene from castor bean (Ricinus communis L. cv. Hale). The PLD gene was isolated from a castor bean genomic library using the PLD cDNA as a hybridization probe. Sequence comparison with the PLD cDNA revealed that the PLD gene consisted of four exons and three introns, one of which interrupts the 5'-untranslated region. Southern blot analysis indicated that the cloned PLD gene was present as a single-copy gene, and yet there were other PLD or PLD-related sequences in the castor bean genome.
Plant Mol Biol 1996 Nov
PMID:Structure and analysis of phospholipase D gene from Ricinus communis L. 898 May 29

The transphosphatidylation reaction is a unique property of phospholipase D (PLD). In this study, the abilities of plant and mammalian PLDs to utilize straight chain and branched alcohols for transphosphatidylation were analyzed and compared. PLD from peanut utilizes C1 to C8 primary alcohols and gives maximal reaction with butanol. In contrast, PLD from A7r5 vascular smooth muscle cells gives maximal reaction with pentanol and does not utilize octanol. Secondary and tertiary alcohols are not substrates for either enzyme. For branched alcohols, activity increases with distance from the alcohol to the branch point. Competition studies indicated that secondary alcohols cannot access the binding pocket. Thus, PLDs have a water/alcohol binding site with defined steric and hydrophobic parameters.
Biochem Mol Biol Int 1997 Apr
PMID:Utilization of alcohols by plant and mammalian phospholipase D. 911 33

The physiological activator of protein kinase C (PKC), diacylglycerol, is formed by hydrolysis of phosphoinositides (PI) by phospholipase C (PLC) or phosphatidylcholine by phospholipase D (PLD). We have measured activation of these phospholipases by endothelin-1 (ET-1), bradykinin (BK), or phenylephrine (PE) in ventricular myocytes cultured from neonatal rat. The stimulation of PI hydrolysis after 10 min by 0.1 microM ET-1 (about 12-fold) was much greater than for BK or PE (each about four-fold), and did not correlate with translocation of nPKC delta or nPKC epsilon (Clerk A. Bogoyevitch MA. Andersson MB. Sugden PH, 1994. J Biol Chem 269: 32848-32857: Clerk A, Gillespie-Brown J, Fuller SJ, Sugden PH, 1996. Biochem J 317: 109-118). However, ET-1 and BK stimulated a similar rapid increase in [3H]InsP, formation (< 30 s), which was much greater than that seen with PE. This early phase correlated with PKC translocation. Acute or chronic exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) or treatment with Ro-31-8220 showed that the stimulation of PI hydrolysis by PE, but not ET-1 or BK, was inhibited by activation of PKC. Furthermore, ET-1 and BK heterologously desensitized the stimulation of PI hydrolysis by PE, ET-1 or BK homologously uncoupled their own receptors from [3H]InsP3 formation, but there was no evidence of heterologous desensitization with these two agonists. Anomalously, chronic exposure to TPA increased the stimulation of PI hydrolysis by BK, but this probably resulted from an increase in BK receptor density. PLD was also rapidly activated by TPA. ET-1, BK or PE. Experiments with Ro-31-8220 showed that the stimulation of PLD by ET-1 and BK was mediated through activation of PKC. We discuss the characteristics of the activation of PI hydrolysis and PLD by ET-1, BK, and PE with respect to the translocation of PKC.
J Mol Cell Cardiol 1997 Jun
PMID:Regulation of phospholipases C and D in rat ventricular myocytes: stimulation by endothelin-1, bradykinin and phenylephrine. 922 Mar 45

Using human spermatozoa stimulated with either progesterone or the Ca2+ ionophore A23187 to undergo acrosomal exocytosis, we have investigated potential pathways for generation of diacylglycerol (DAG) and have examined the possibility that DAG plays an important role in the exocytotic response. Both treatments resulted in rapid and considerable generation of DAG, followed by a limited rise in phosphatidic acid (PA). Further experiments indicated that phospholipase C (PLC) activity is important in this generation of DAG, but phospholipase D activity probably is not. In addition, polyphosphoinositide-specific phosphoinositidase C activation and hydrolysis, of phosphatidylinositol 4,5-bisphosphate appears to be a necessary prerequisite for activation of the PLC pathway. Finally the DAG formed appears to be important in acrosomal exocytosis: (i) blocking DAG metabolism with a DAG kinase inhibitor resulted in both increased endogenous levels of DAG and a significantly increased exocytotic response in stimulated cells and (ii) exogenous DAG induced exocytosis in capacitated spermatozoa whereas PA did not. Taken together, these results suggest that DAG plays a key role in events leading to membrane fusion during human sperm acrosomal exocytosis stimulated by natural agonists.
Mol Hum Reprod 1996 May
PMID:A role for diacylglycerol in human sperm acrosomal exocytosis. 923 98

sn-1,2-Diacylglycerol (DAG) mass and translocation of protein kinase C alpha and beta to a membrane fraction increased approximately 7 min after insemination of Xenopus laevis eggs. The DAG mass increase of 48 pmol (from 62 to 110 pmol/cell) was greater than that for inositol 1,4,5-trisphosphate (IP3; an increase of approximately 170 fmol or approximately 280-fold smaller than the DAG increase), and DAG peaks approximately 5 min after IP3. Choline mass (a measure of phosphatidyl choline-specific phospholipase D) also peaked before DAG and the choline increase (134 pmol/cell) was greater than that of DAG. There was no detectable change in phosphocholine mass (a measure of phosphatidylcholine-specific phospholipase C). During first cleavage, DAG decreased, PKC translocation was low, and choline increased and peaked (whereas published work shows an increase in IP3 mass). Artificial elevation of intracellular calcium ([Ca2+]i) increased DAG levels but prevention of the [Ca2+]i increase after fertilization did not block DAG production. Thus, sperm stimulate production of DAG and choline through [Ca2+]i-independent and [Ca2+]i-dependent paths.
Mol Biol Cell 1997 Apr
PMID:sn-1,2-diacylglycerol and choline increase after fertilization in Xenopus laevis. 924 52

Swiss 3T3 fibroblasts were treated with the microtubule-disrupting agent colchicine to study any interaction between microtubule dynamics and actin polymerization. Colchicine increased the amount of filamentous actin (F-actin), in a dose- and time-dependent manner with a significant increase at 1 h by about 130% over control level. Confocal microscopic observation showed that colchicine increased F-actin contents by stress fiber formation without inducing membrane ruffling. Colchicine did not activate phospholipase C and phospholipase D, whereas lysophosphatidic acid did, indicating that colchicine may have a different mechanism of actin polymerization regulation from LPA. A variety of microtubule-disrupting agents stimulated actin polymerization in Swiss 3T3 and Rat-2 fibroblasts as did colchicine, but the microtubule-stabilizing agent taxol inhibited actin polymerization induced by the above microtubule-disrupting agents. In addition, colchicine-induced actin polymerization was blocked by two protein phosphatase inhibitors, okadaic acid and calyculin A. These results suggest that microtubule depolymerization activates stress fiber formation by serine/threonine dephosphorylation in fibroblasts.
Mol Cells 1997 Jun 30
PMID:Colchicine activates actin polymerization by microtubule depolymerization. 926 34

We have previously reported that endothelial cell phospholipase D (PLD), activated by 4-hydroxynonenal (4-HNE), was independent of protein kinase C activation. To determine whether PLD stimulation by 4-HNE is related to protein tyrosine phosphorylation, the effects of tyrosine kinase (Tyrk) and protein tyrosine phosphatase (PTPase) inhibitors on PLD activation were investigated. Pretreatment of bovine pulmonary artery endothelial cells (BPAEC) with Tyrk inhibitors, such as genistein, erbstatin, and herbimycin attenuated 4-HNE-induced PLD activation. Furthermore, vanadate, phenylarsine oxide, and diamide, inhibitors of PTPases, markedly increased the 4-HNE-induced PLD activation. The effects of Tyrk and PTPase inhibitors were specific towards the 4-HNE, as these agents had no effect on the agonist- or TPA-induced PLD activation. In addition to PLD activation, treatment of BPAEC with 4-HNE increased tyrosine phosphorylation of proteins including bands of molecular weights 40,000-60,000, 70,000-90,000, and 110,000-130,000. The 4-HNE-mediated increase in protein tyrosine phosphorylation was partly inhibited by genistein (100 microM). Vanadate (10 microM) pretreatment also potentiated 4-HNE-induced protein tyrosine phosphorylation. These data suggest that 4-HNE-mediated stimulation of PLD may occur as a result of activation of tyrosine kinases.
Am J Respir Cell Mol Biol 1997 Aug
PMID:Phosphatase inhibitors potentiate 4-hydroxynonenal-induced phospholipase D activation in vascular endothelial cells. 927 14

Phospholipase C-beta (PLC-beta) signalling via protein kinase C (PKC) has been recognized as a major route by which stimuli such as alpha1-adrenergic agonists, endothelin-1 (ET-1) and angiotensin II (Ang II) induce hypertrophy of myocytes. The goal of this study was to evaluate the role of phospholipase D (PLD) in contributing to the formation of the PKC activator 1,2-diacylglycerol (1,2-DAG) and to study the mechanism(s) of PLD activation by agonists. Stimulation of serum-free cultured neonatal rat cardiomyocytes with ET-1 (10(-8)M), phenylephrine (PHE, 10(-5)M) or Ang II (10(-7)M) resulted in a rapid (0-10 min) activation of PLC-beta to an extent (ET-1>PHE>Ang II) that correlated with the magnitude of stimulation of protein synthesis ([3H]leucine incorporation into protein) measured after 24 h. Phorbol 12-myristate 13-acetate (PMA, 10(-6)M) and ET-1 were equipotent in stimulating protein synthesis. ET-1 and PMA, but not PHE and Ang II stimulated [3H]choline formation from labelled PtdCho after a lag-phase of about 10 min. That this [3H]choline formation was due to the action of PLD was confirmed by measurement of phosphatidylgroup-transfer from cellular [14C]palmitoyl-phosphatidylcholine to exogenous ethanol. ET-1 and PHE, to much lesser extent, produced a rapid (0-5 min) translocation of PKC- immunoreactivity from the cytosol to the membrane fraction, whereas no intracellular redistribution of PKC-alpha, -delta and -xi immunoreactivities was observed. PMA caused translocation of PKC-alpha, PKC-epsilon as well as PKC-delta. Cellular redistribution of PKC activity measured by [32P]-incorporation into histone III-S was not observed with ET-1 and PHE, but only with PMA stimulation. Down-regulation of PKC isozymes by 24 h pretreatment of cells with PMA or blockade of PKC by chelerythrine (10(-4)M) inhibited ET-1 and PMA stimulated [3H]choline production. Staurosporine (10(-6)M) had, however, no effect. In conclusion, the results indicate that in serum-free cultured cardiomyocytes, ET-1 initially activates PLC-beta and after a lag-phase PLD, whereas PHE and Ang II activate only PLC-beta. PLC-beta stimulated by ET-1, may cross-talk with PLD via translocation of PKC-epsilon. These signals are possibly linked to the hypertrophic response.
J Mol Cell Cardiol 1997 Sep
PMID:Cross-talk between receptor-mediated phospholipase C-beta and D via protein kinase C as intracellular signal possibly leading to hypertrophy in serum-free cultured cardiomyocytes. 929 77

Phosphatidic acid (PA) is mainly formed by the hydrolysis of phosphatidylcholine due to the activation of phospholipase D (PLD). PA is also generated by phosphorylation of diacylglycerol (DAG) due to the action of DAG kinase and is converted to DAG under the action of PA phosphohydrolase. Most of the positive inotropic agents which are known to stimulate cardiac hypertrophy, have been shown to increase the level of PA in cardiac sarcolemma. Although the growth factor-like effect of PA has been recognized in a wide variety of tissues, there is a lack of similar information in adult cardiomyocytes. By using single cardiomyocytes, we have now shown that PA increased the basal [Ca2+]i level without significant effect on the amplitude of Ca2+ transients. PA (10-50 mu M) also increased the [Ca2+]i in cardiac cell suspension. PA has also been shown to stimulate protein synthesis in cardiomyocytes, which is inhibited by a PKC inhibitor as well as a Ca2+ chelator. PA at the concentration of 1-50 mu M was observed to stimulate the activity of PLC in cardiac sarcolemma; this effect was attenuated by a PLC inhibitor. Since DAG, formed due to the activation of PLC, is considered to play a crucial role in regulating the activity of protein kinase C (PKC), the positive feedback effect of PA on this pathway may be essential for maintaining the sustained elevation in the activity of PKC during the development of cardiac hypertrophy. In view of these observations and other facts available in the literature, it is suggested that PA may be a potential signal transducer for the development of cardiac hypertrophy.
J Mol Cell Cardiol 1997 Nov
PMID:Phosphatidic acid: a potential signal transducer for cardiac hypertrophy. 940 62


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